Relationship between preoperative dental anxiety and short-term inflammatory response following oral surgery.

BACKGROUND: The relationship between dental anxiety and mucosal wound healing, especially the inflammatory response, has not been well studied. This study aimed to examine the relationship between anxiety prior to dental treatment and short-term inflammation following impacted mandibular third molar (IMTM) surgery. METHODS: Fifty-nine patients who required IMTM surgery were recruited for this study. Sample demographics (gender, age) and surgical extent (Pederson classification, duration) were collected. Psychological stress towards surgery was assessed by the Dental Fear Survey (DFS). All surgeries were conducted according to an identical surgical protocol and all patients were given the same medical prescription. Correlations between short-term inflammation (swelling and trismus after 2 days) and DFS, demographics and surgical extent were statistically analysed. RESULTS: The results showed that patients with a higher DFS score demonstrated more severe swelling (ß = 0.36, P = 0.016) and trismus (ß = 0.37, P = 0.008) 2 days after surgery. In addition, more severe trismus occurred following more difficult surgery (ß = 0.29, P = 0.016) or that with a longer duration (ß = 0.21, P = 0.081). Neither gender nor age showed any significant relationship with swelling or trismus. CONCLUSION: Short-term inflammatory response following IMTM surgery correlated with the preoperative dental anxiety and this correlation was independent of gender and surgical extent.

Measurement of zinc concentration in blood and breast milk of a Wilson's disease patient taking zinc acetate.

Case: A 27-year-old, gravida 2, para 0, Japanese female who was maintained on zinc acetate (75 mg/day) during pregnancy expressed her desire to breastfeed after birth. We investigated the possibility of breastfeeding while on treatment. Breast milk zinc concentrations were determined using an atomic absorption photometer. Breast milk zinc concentrations on the 4th (colostrum) and 32nd (post-colostrum) days post partum were 10.80 µg/mL and 3.28 µg/mL, respectively. These values are less than the reported range of breast milk zinc concentrations in Japanese women who are not under any medication. Conclusion: We measured blood and breast milk zinc concentrations of a patient with Wilson's disease who was taking zinc acetate (75 mg/day). Zinc values were within the range of breast milk concentrations of mothers who are not on zinc acetate.

Exposure to Asian dust within a few days of delivery is associated with placental abruption in Japan: a case-crossover study.

OBJECTIVE: Asian dust is a natural phenomenon in which dust particles are transported from desert areas in China and Mongolia to East Asia. Short-term exposure to Asian dust has been associated with cardiovascular disease through mechanisms such as systemic inflammation. Because inflammation is a potential trigger of placental abruption, exposure may also lead to abruption. We examined whether exposure to Asian dust was associated with abruption. DESIGN: A bi-directional, time-stratified case-crossover design. SETTING AND POPULATION: From the Japan Perinatal Registry Network database, we identified 3014 patients who delivered singleton births in hospitals in nine Japanese prefectures from 2009 to 2014 with a diagnosis of placental abruption. METHODS: Asian dust levels were measured at Light Detection and Ranging monitoring stations, and these measurements were used to define the Asian dust days. As there was no information on the onset day of abruption, we assumed this day was the day before delivery (lag1). MAIN OUTCOME MEASURES: Placental abruption. RESULTS: During the study period, the Asian dust days ranged from 15 to 71 days, depending on the prefecture. The adjusted odds ratio of placental abruption associated with exposure to Asian dust was 1.4 (95% confidence interval = 1.0, 2.0) for cumulative lags of 1-2 days. Even after adjustment for co-pollutant exposures, this association did not change substantially. CONCLUSIONS: In this Japanese multi-area study, exposure to Asian dust was associated with an increased risk of placental abruption. TWEETABLE ABSTRACT: Exposure to environmental factors such as Asian dust may be a trigger of placental abruption.

Stability of cervical esophagogastrostomy via hand-sewn anastomosis after esophagectomy for esophageal cancer.

The aim of the present study is to evaluate the outcome of hand-sewn esophagogastric anastomosis during radical esophagectomy for esophageal cancer. The outcomes of 467 consecutive esophageal cancer patients who underwent cervical esophagogastric anastomosis using interrupted and double-layered sutures after radical esophagectomy via right thoracotomy or thoracoscopic surgery were retrospectively reviewed. Anastomotic leakage, including conduit necrosis, occurred in 11 of 467 patients (2.4%); 7 of 11 (63.6%) cases experienced only minor leakage, whereas the other four (36.4%) patients had major leakage that required surgical or radiologic intervention, including two patients of conduit necrosis. Anastomotic leakages were more frequently observed after retrosternal reconstruction compared with the posterior mediastinal route (P < 0.0001). The median time to healing of leakage was 40 days (range: 14-97 days). Two patients (2/467, 0.4%) died in the hospital due to sepsis caused by the leakage and conduit necrosis. Twelve patients (2.6%) developed anastomotic stenosis, which was improved by dilatation in all patients. Hand-sewn cervical esophagogastric anastomosis is a stable and highly safe method of radical esophagectomy for esophageal cancer.

A Distinct Subpopulation of Bone Marrow Mesenchymal Stem Cells, Muse Cells, Directly Commit to the Replacement of Liver Components.

Genotyping graft livers by short tandem repeats after human living-donor liver transplantation (n = 20) revealed the presence of recipient or chimeric genotype cases in hepatocytes (6 of 17, 35.3%), sinusoidal cells (18 of 18, 100%), cholangiocytes (15 of 17, 88.2%) and cells in the periportal areas (7 of 8, 87.5%), suggesting extrahepatic cell involvement in liver regeneration. Regarding extrahepatic origin, bone marrow mesenchymal stem cells (BM-MSCs) have been suggested to contribute to liver regeneration but compose a heterogeneous population. We focused on a more specific subpopulation (1-2% of BM-MSCs), called multilineage-differentiating stress-enduring (Muse) cells, for their ability to differentiate into liver-lineage cells and repair tissue. We generated a physical partial hepatectomy model in immunodeficient mice and injected green fluorescent protein (GFP)-labeled human BM-MSC Muse cells intravenously (n = 20). Immunohistochemistry, fluorescence in situ hybridization and species-specific polymerase chain reaction revealed that they integrated into regenerating areas and expressed liver progenitor markers during the early phase and then differentiated spontaneously into major liver components, including hepatocytes (≈74.3% of GFP-positive integrated Muse cells), cholangiocytes (≈17.7%), sinusoidal endothelial cells (≈2.0%), and Kupffer cells (≈6.0%). In contrast, the remaining cells in the BM-MSCs were not detected in the liver for up to 4 weeks. These results suggest that Muse cells are the predominant population of BM-MSCs that are capable of replacing major liver components during liver regeneration.

miR-9-3p plays a tumour-suppressor role by targeting TAZ (WWTR1) in hepatocellular carcinoma cells.

BACKGROUND: The inactivation of the Hippo pathway lead to TAZ (PDZ-binding motif)/YAP (yes-associated protein) overexpression, and is associated with worse prognostic outcomes in various cancers including hepatocellular carcinoma (HCC). Although there are several reports of microRNA (miR) targeting for YAP, miR targeting for TAZ remains unclear. The aim of this study is to identify the miR targeting TAZ expression in HCC. METHODS: MicroRNA expression was analysed using the Human miFinder 384HC miScript miR PCR array, and was compared between low and high TAZ expression cell lines. Then, we extracted miR-9-3p as a tumour-suppressor miR targeting TAZ. We examined the functional role of miR-9-3p using miR-9-3p mimic and inhibitor in HCC cell lines). RESULTS: In HCC cell lines and HCC clinical samples, there was the inverse correlation between miR-9-3p and TAZ expressions. TAZ expression was induced by treatment of miR-9-3p inhibitor and was downregulated by treatment of miR-9-3p mimic. Treatment of miR-9-3p mimic inhibited cell proliferative ability with downregulated phosphorylations of Erk1/2, AKT, and ß-catenin in HLF. Inversely, treatment of miR-9-3p inhibitor accelerated cell growth compared with control in HuH1. CONCLUSIONS: MicroRNA-9-3p was identified as the tumour-suppressor miR targetting TAZ expression in HCC cells.

Effect of LSKL peptide on thrombospondin 1-mediated transforming growth factor ß signal activation and liver regeneration after hepatectomy in an experimental model.

BACKGROUND: A strategy for accelerating liver regeneration after hepatectomy would offer great benefits in preventing postoperative liver failure and improving surgical outcomes. Transforming growth factor (TGF) ß is a potent inhibitor of hepatocyte proliferation. Recently, thrombospondin (TSP) 1 has been identified as a negative regulator of liver regeneration by activation of local TGF-ß signals. This study aimed to clarify whether the LSKL (leucine-serine-lysine-leucine) peptide, which inhibits TSP-1-mediated TGF-ß activation, promotes liver regeneration after hepatectomy in mice. METHODS: Mice were operated on with a 70 per cent hepatectomy or sham procedure. Operated mice received either LSKL peptide or normal saline intraperitoneally at abdominal closure and 6 h after hepatectomy. Perioperative plasma TSP-1 levels were measured by enzyme-linked immunosorbent assay in patients undergoing hepatectomy. RESULTS: Administration of LSKL peptide attenuated Smad2 phosphorylation at 6 h. S-phase entry of hepatocytes was accelerated at 24 and 48 h by LSKL peptide, which resulted in faster recovery of the residual liver and bodyweight. Haematoxylin and eosin tissue staining and blood biochemical examinations revealed no significant adverse effects following the two LSKL peptide administrations. In the clinical setting, plasma TSP-1 levels were lowest on the first day after hepatectomy. However, plasma TSP-1 levels at this stage were significantly higher in patients with subsequent liver dysfunction compared with levels in those without liver dysfunction following hepatectomy. CONCLUSION: Only two doses of LSKL peptide during the early period after hepatectomy can promote liver regeneration. The transient inhibition of TSP-1/TGF-ß signal activation using LSKL peptide soon after hepatectomy may be a promising strategy to promote subsequent liver regeneration. Surgical relevance Although the mechanisms of liver regeneration after hepatectomy have been explored intensively in vivo, no therapeutic tools are thus far available to accelerate liver regeneration after hepatectomy in the clinical setting. Recently, the matricellular protein thrombospondin (TSP) 1, a major activator of latent transforming growth factor (TGF) ß1, has been identified as a negative regulator of liver regeneration after hepatectomy. In this study, the inhibition of TSP-1-mediated TGF-ß signal activation by LSKL (leucine-serine-lysine-leucine) peptide in the early period after hepatectomy accelerated liver regeneration without any adverse effects. In addition, continuous high plasma TSP-1 levels after hepatectomy were associated with liver damage in humans. The transient inhibition of TSP-1/TGF-ß signal activation using LSKL peptide in the early period after hepatectomy could be a novel therapeutic strategy to accelerate liver regeneration after hepatectomy.

CD44s signals the acquisition of the mesenchymal phenotype required for anchorage-independent cell survival in hepatocellular carcinoma.

BACKGROUND: Circulating tumour cells (CTCs) have an important role in metastatic processes, but details of their basic characteristics remain elusive. We hypothesised that CD44-expressing CTCs show a mesenchymal phenotype and high potential for survival in hepatocellular carcinoma (HCC). METHODS: Circulating CD44(+)CD90(+) cells, previously shown to be tumour-initiating cells, were sorted from human blood and their genetic characteristics were compared with those of tumour cells from primary tissues. The mechanism underlying the high survival potential of CD44-expressing cells in the circulatory system was investigated in vitro. RESULTS: CD44(+)CD90(+) cells in the blood acquired epithelial-mesenchymal transition, and CD44 expression remarkably increased from the tissue to the blood. In Li7 and HLE cells, the CD44(high) population showed higher anoikis resistance and sphere-forming ability than did the CD44(low) population. This difference was found to be attributed to the upregulation of Twist1 and Akt signal in the CD44(high) population. Twist1 knockdown showed remarkable reduction in anoikis resistance, sphere formation, and Akt signal in HLE cells. In addition, mesenchymal markers and CD44s expression were downregulated in the Twist1 knockdown. CONCLUSIONS: CD44s symbolises the acquisition of a mesenchymal phenotype regulating anchorage-independent capacity. CD44s-expressing tumour cells in peripheral blood are clinically important therapeutic targets in HCC.

Protein expression and gene copy number changes of receptor tyrosine kinase in thymomas and thymic carcinomas.

BACKGROUND: Insulin-like growth factor-1 receptor (IGF-1R), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-type 2 (HER2), and c-Met are members of the receptor tyrosine kinases (RTKs). The associations between the RTK status [protein expression and gene copy number (GCN)] and patient characteristics and between the RTK status and prognosis remain undetermined. MATERIALS AND METHODS: The study included 140 patients who underwent surgery for thymic tumors. Protein expression was evaluated by immunohistochemistry (IHC) and GCN was evaluated by bright-field in situ hybridization (BISH). The correlations between the RTK status and clinicopathological findings were examined. RESULTS: IGF-1R protein was frequently detected in thymic carcinoma (83.8%) and EGFR in thymic tumors (91.4%). Thirty-six and 39 tumors were BISH high for IGF-1R and EGFR, respectively: 28 and 25 exhibited high polysomy; 8 and 14 exhibited gene amplification. No tumor was positive for HER2 or c-Met by IHC and BISH. Multivariate analysis revealed that IGF-1R gene amplification (P = 0.027), thymic carcinoma histology, and higher tumor stage were significantly correlated with an adverse prognosis. CONCLUSIONS: Thymic epithelial tumors frequently express IGF-1R and/or EGFR proteins. IGF-1R gene amplification is suggested to define an unfavorable subset for thymic epithelial tumors.

Using sorafenib for recurrent hepatocellular carcinoma after liver transplantation--interactions between calcineurin inhibitor: two case reports.

No effective therapeutic approaches have been available for early recurrences following liver transplantation for hepatocellular carcinoma (HCC). The prognosis for such patients has been poor. We encountered two patients with recurrent HCC following liver transplantation, and in the prescribed sorafenib after the failure of various therapeutic approaches. In vitro experiments have shown sorafenib to be metabolized by the drug-metabolizing enzyme cytochrome P450 3A4 (CYP3A4) and glucuronosyltransferase (UGT1A9). The metabolic pathway is predicted to overlap that of calcineurin inhibitors (CNIs). In the two cases in which we used sorafenib, tacrolimus (FK506) was used in case 1 and cyclosporine, in case 2. We therefore have also reported the blood levels of the CNI at the time of sorafenib use. Patients with recurrent HCC following liver transplantation were less tolerant of sorafenib than advanced HCC patients who had not undergone transplantation. Poor tolerance was believed to be due to pharmacological interactions of sorafenib and CNIs. Likewise in our patients, determining blood levels of sorafenib, including the area under the blood concentration-time curve of at least the CNI, in each case allowed us to determine the optimal sorafenib dose for each patient. In the future, when administering sorafenib to treat recurrent liver cancers following liver transplantation, the dose of sorafenib should be started at 200 mg/d and gradually increased while measuring CNI blood levels.

Laparoscopy-assisted appendectomy through an umbilical port in children.

INTRODUCTION: We report surgical techniques for single-incision laparoscopy-assisted surgery (SILAS) in the treatment of pediatric acute appendicitis. METHODS: We performed SILAS in 15 cases of acute appendicitis between January and September of 2009. SILAS is a surgical method that involves making the incision at the umbilicus, inserting a wound retractor XS, suspending the abdominal wall with a hook, and appendectomy with the same procedures as conventional appendectomy. RESULTS: SILAS appendectomy was performed in all 15 cases with the exception of one case where one 3-mm port was added. Compared to open appendectomy, blood loss was significantly lower and postoperative hospitalization time was shorter, although there was no significant decrease in operative time, or postoperative fasting time. No postoperative complications, such as wound infection, intestinal obstruction, intra-abdominal abscess, or bleeding, were encountered. CONCLUSION: SILAS was safely performed and is superior to open appendectomy with regard to cosmetic outcome.

Minimally invasive surgical enucleation for esophageal leiomyoma: report of seven cases.

Benign esophageal tumor is a rare entity, with leiomyoma being the most common lesion. We present our experience with enucleation of esophageal leiomyomas using a minimally invasive approach. Between March 1998 and June 2008, seven patients with esophageal leiomyoma underwent right thoracosopic enucleation (n=4) or laparoscopic transhiatal enucleation (n=3). A Dor (n=2) or Toupet fundoplication (n=1) were added for laparoscopic procedure. The mean tumor size was 3.9 cm (range, 1.5-5.5 cm). Tumor locations were upper (n=2), middle (n=1), and lower (n=4) thirds of the esophagus. No major morbidities including postoperative leakage or mortalities occurred. At a mean follow-up period of 60.1 months (range, 14-260 months), no evidence of recurrences were observed. Thoracoscopic and laparoscopic transhiatal enucleation for esophageal leiomyomas is a safe and feasible procedure. The optimal approaches should be tailored based on the location and size of the tumor.

Regulatory roles of beta-catenin and AP-1 on osteoprotegerin production in interleukin-1alpha-stimulated periodontal ligament cells.

BACKGROUND: Periodontitis is a chronic inflammatory disease characterized by the enhanced expression of inflammatory mediators leading to alveolar bone resorption. Osteoprotegerin (OPG) plays a suppressive role in cytokine-induced osteoclastogenesis. In osteoblasts, OPG expression is upregulated by beta-catenin but downregulated by the transcription factor activator protein-1 (AP-1; c-fos/c-jun). The purpose of this study was to examine the roles of beta-catenin and AP-1 in interleukin-1alpha (IL-1alpha) -induced OPG production in human gingival fibroblasts (hGFs) and periodontal ligament (PDL) cells. METHODS: Expression of c-fos and c-jun messenger RNA was measured by reverse transcription-polymerase chain reaction and OPG production was analysed by enzyme-linked immunosorbent assay. The nuclear AP-1 activity was quantified using an AP-1 microplate assay. The effect of the Wnt canonical pathway on OPG production was evaluated using small interfering (si) RNA for beta-catenin and the effect of AP-1 on OPG production was evaluated using the AP-1 inhibitor curcumin. RESULTS: Levels of c-fos messenger RNA and nuclear AP-1 activity were higher in PDL cells than in hGFs. When stimulated with IL-1alpha, PDL cells had significantly higher c-fos expression and lower OPG production compared with hGFs. The siRNA for beta-catenin suppressed the IL-1alpha-induced OPG production in both PDL cells and hGFs, whereas the AP-1 inhibitor curcumin augmented the IL-1alpha-induced OPG production in PDL cells, but not in hGFs. CONCLUSION: The present study suggests that beta-catenin enhances IL-1alpha-induced OPG production in both PDL cells and hGFs, whereas AP-1 suppresses IL-1alpha-induced OPG production in PDL cells. Higher expression of c-fos in PDL cells than in hGFs may implicate a role of PDL cells in alveolar bone resorption in periodontitis.

Ten-year experience of totally laparoscopic liver resection in a single institution.

BACKGROUND: Recent developments in liver surgery include the introduction of laparoscopic liver resection. The aim of the present study was to review a single institution's 10-year experience of totally laparoscopic liver resection (TLLR). METHODS: Between May 1997 and April 2008, 82 patients underwent TLLR for hepatocellular carcinoma (HCC) (37 patients), liver metastases (39) and benign liver lesions (six). Operations included 69 laparoscopic wedge resections, 11 laparoscopic left lateral sectionectomies and two thoracoscopic wedge resections. Nine patients underwent simultaneous laparoscopic resection of colorectal primary cancer and synchronous liver metastases. RESULTS: Median operating time was 177 (range 70-430) min and blood loss 64 (range 1-917) ml. Median tumour size and surgical margin were 25 (range 15-85) and 6 (range 0-40) mm respectively. One procedure was converted to a laparoscopically assisted hepatectomy. Three patients developed complications. Median postoperative stay was 9 (range 3-37) days. The overall 5-year survival rate after surgery for HCC and colorectal metastases was 53 and 64 per cent respectively. CONCLUSION: TLLR can be performed safely for a variety of primary and secondary liver tumours, and seems to offer at least short-term benefits in selected patients.

Multi-center intervention study on glycohemoglobin (HbA1c) and serum, high-sensitivity CRP (hs-CRP) after local anti-infectious periodontal treatment in type 2 diabetic patients with periodontal disease.

The purpose of this study was to examine whether periodontal treatment incorporating topical antibiotic therapy affects on levels of glycohemoglobin (HbA1c) and serum high-sensitivity C-reactive protein (hs-CRP) in type 2 diabetic patients with periodontal disease, and to explore the relationship between CRP and glycemic control. The whole intervention group (n=32), which underwent anti-infectious periodontal treatment, showed only transient reduction in HbA1c levels without any change in hs-CRP, while the control group (n=17) did not show any changes in HbA1c or hs-CRP. Multiple regression analysis of all subjects revealed that BMI and change in hs-CRP correlated significantly with the reduction of HbA1c at 6 months after the periodontal treatment. Based on the results of multiple regression analysis, the intervention group was subdivided into two groups: those in which hs-CRP levels decreased (CRP-D group), and those in which hs-CRP levels unchanged or increased (CRP-N group) (n=16, respectively), and re-analysis was conducted based upon these subgroups. In the CRP-D subgroup, HbA1c was significantly reduced at the end of the study, but it did not decrease in the CRP-N subgroup. The decrease of HbA1c in the CRP-D subgroup following periodontal treatment was significantly greater than that in the CRP-N subgroup. BMI of each group remained unchanged in this study at the end of the study. Thus, the results suggested that periodontal treatment with topical antibiotics improves HbA1c through reduction of CRP, which may relate to amelioration of insulin resistance, in type 2 diabetic patients with periodontal disease.